Expression profiling by high-throughput sequencing reveals GADD45, SMAD7, EGR-1 and HOXA3 activation in Myostatin (MSTN) and GDF11 treated myoblasts.

Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor ß (TGFß) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research.

New dienelactone hydrolase from microalgae bacterial community-Antibiofilm activity against fish pathogens and potential applications for aquaculture.

Biofilms are resistant to many traditional antibiotics, which has led to search for new antimicrobials from different and unique sources. To harness the potential of aquatic microbial resources, we analyzed the meta-omics datasets of microalgae-bacteria communities and mined them for potential antimicrobial and quorum quenching enzymes. One of the most interesting candidates (Dlh3), a dienelactone hydrolase, is a α/ß-protein with predicted eight α-helices and eight ß-sheets. When it was applied to one of the major fish pathogens, Edwardsiella anguillarum, the biofilm development was reproducibly inhibited by up to 54.5%. The transcriptome dataset in presence of Dlh3 showed an upregulation in functions related to self-defense like active genes for export mechanisms and transport systems. The most interesting point regarding the biotechnological potential for aquaculture applications of Dlh3 are clear evidence of biofilm inhibition and that health and division of a relevant fish cell model (CHSE-214) was not impaired by the enzyme.

Intestinal epithelia and myeloid immune cells shape colitis severity and colorectal carcinogenesis via High-mobility group box protein 1.

BACKGROUND: HMGB1 is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and infectious inflammation. Stool and serum HMGB1 levels correlate with colitis severity and colorectal cancer (CRC) progression, yet recent reports indicated HMGB1 to mainly operate as an intracellular determinant of enterocyte fate during colitis, and investigations into the roles of HMGB1 in CRC are lacking. Using mice with conditional HMGB1-knockout in enterocytes (Hmgb1ΔIEC) and myeloid cells (Hmgb1ΔLysM), respectively, we explored functions of HMGB1 in pathogenetically diverse contexts of colitis and colitis-associated CRC. RESULTS: HMGB1 is overexpressed in human inflammatory bowel disease and gastrointestinal cancers, and HMGB1 protein localizes in enterocytes and stromal cells in colitis and CRC specimens from humans and rodents. As previously described, enterocyte HMGB1 deficiency aggravates severe chemical-induced intestinal injury, but not Citrobacter rodentium or T cell transfer colitis in mice. HMGB1-deficient enterocytes and organoids do not exhibit deviant apoptotic or autophagic activity, altered proliferative or migratory capacity, abnormal intestinal permeability or aberrant DSS-induced organoid inflammation in vitro. Instead, we observed altered in vivo-reprogramming of both intestinal epithelia and infiltrating myeloid cells in Hmgb1ΔIEC early during colitis, suggesting HMGB1-mediated paracrine injury signaling. Hmgb1ΔIEC had higher CRC burden than wildtypes in the Apc+/min model, whereas inflammatory CRC was attenuated in Hmgb1ΔLysM. Cellular and molecular phenotyping of Hmgb1ΔIEC and Hmgb1ΔLysM cancers indicates context-dependent transcriptional modulation of immune signaling and extracellular matrix remodeling via HMGB1. CONCLUSION: Enterocytes and myeloid cells context-dependently regulate host responses to severe colitis and maladaptive intestinal wound healing via HMGB1.

Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid.

BACKGROUND: Molecular brain tumor diagnosis is usually dependent on tissue biopsies or resections. This can pose several risks associated with anesthesia or neurosurgery, especially for lesions in the brain stem or other difficult-to-reach anatomical sites. Apart from initial diagnosis, tumor progression, recurrence, or the acquisition of novel genetic alterations can only be proven by re-biopsies. METHODS: We employed Nanopore sequencing on cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and analyzed copy number variations (CNV) and global DNA methylation using a random forest classifier. We sequenced 129 samples with sufficient DNA. These samples came from 99 patients and encompassed 22 entities. Results were compared to clinical diagnosis and molecular analysis of tumor tissue, if available. RESULTS: 110/129 samples were technically successful, and 50 of these contained detectable circulating tumor DNA (ctDNA) by CNV or methylation profiling. ctDNA was detected in samples from patients with progressive disease but also from patients without known residual disease. CNV plots showed diagnostic and prognostic alterations, such as C19MC amplifications in embryonal tumors with multilayered rosettes or Chr.1q gains and Chr.6q losses in posterior fossa group A ependymoma, respectively. Most CNV profiles mirrored the profiles of the respective tumor tissue. DNA methylation allowed exact classification of the tumor in 22/110 cases and led to incorrect classification in 2/110 cases. Only 5/50 samples with detected ctDNA contained tumor cells detectable through microscopy. CONCLUSIONS: Our results suggest that Nanopore sequencing data of cfDNA from CSF samples may be a promising approach for initial brain tumor diagnostics and an important tool for disease monitoring.

Stenotrophomonas maltophilia affects the gene expression profiles of the major pathogens Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro multispecies biofilm model.

IMPORTANCE: In the past, studies have focused on bacterial pathogenicity in mono-species infections, in part ignoring the clinical relevance of diseases caused by more than one pathogen (i.e., polymicrobial infections). However, it is now common knowledge that multiple bacteria species are often involved in the course of an infection. For treatment of such infections, it is absolutely important to understand the dynamics of species interactions at possible infection sites and the molecular mechanisms behind these interactions. Here, we studied the impact of Stenotrophomonas maltophilia on its commensals Pseudomonas aeruginosa and Staphylococcus aureus in multispecies biofilms. We analyzed the 3D structural architectures of dual- and triple-species biofilms, niche formation within the biofilms, and the interspecies interactions on a molecular level. RNAseq data identified key genes involved in multispecies biofilm formation and interaction as potential drug targets for the clinical combat of multispecies infection with these major pathogens.

Complete genome sequence of a Staphylococcus condimenti isolated from a port catheter-associated bloodstream infection.

Here, we describe the complete genome sequence of a Staphylococcus condimenti blood culture isolate from a catheter-related bloodstream infection in a male patient.

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis.

Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. Methods: The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Discussion: Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.

A deep intronic variant in DNM1 in a patient with developmental and epileptic encephalopathy creates a splice acceptor site and affects only transcript variants including exon 10a.

DNM1 developmental and epileptic encephalopathy (DEE) is characterized by severe to profound intellectual disability, hypotonia, movement disorder, and refractory epilepsy, typically presenting with infantile spasms. Most of the affected individuals had de novo missense variants in DNM1. DNM1 undergoes alternative splicing that results in expression of six different transcript variants. One alternatively spliced region affects the tandemly arranged exons 10a and 10b, producing isoforms DNM1A and DNM1B, respectively. Pathogenic variants in the DNM1 coding region affect all transcript variants. Recently, a de novo DNM1 NM_001288739.1:c.1197-8G > A variant located in intron 9 has been reported in several unrelated individuals with DEE that causes in-frame insertion of two amino acids and leads to disease through a dominant-negative mechanism. We report on a patient with DEE and a de novo DNM1 variant NM_001288739.2:c.1197-46C > G in intron 9, upstream of exon 10a. By RT-PCR and Sanger sequencing using fibroblast-derived cDNA of the patient, we identified aberrantly spliced DNM1 mRNAs with exon 9 spliced to the last 45 nucleotides of intron 9 followed by exon 10a (NM_001288739.2:r.1196_1197ins[1197-1_1197-45]). The encoded DNM1A mutant is predicted to contain 15 novel amino acids between Ile398 and Arg399 [NP_001275668.1:p.(Ile398_Arg399ins15)] and likely functions in a dominant-negative manner, similar to other DNM1 mutants. Our data confirm the importance of the DNM1 isoform A for normal human brain function that is underscored by previously reported predominant expression of DMN1A transcripts in pediatric brain, functional differences of the mouse Dnm1a and Dnm1b isoforms, and the Dnm1 fitful mouse, an epilepsy mouse model.

Murine scald models characterize the role of neutrophils and neutrophil extracellular traps in severe burns.

Introduction: Severe burns cause unique pathophysiological alterations especially on the immune system. A murine scald model was optimized as a basis for the understanding of immunological reactions in response to heat induced injury. The understanding of the roles of neutrophil extracellular traps (NETs) and DNases will support the development of new surgical or pharmacological strategies for the therapy of severe burns. Methods: We studied C57BL/6 mice (n=30) and employed four scalding protocols with varying exposure times to hot water. An additional scald group with a shorter observational time was generated to reduce mortality and study the very early phase of pathophysiology. At 24h or 72h, blood was drawn and tissue (wound, liver, lung, spleen) was analyzed for the presence of NETs, oxidative stress, apoptosis, bacterial translocation, and extracellular matrix re-organization. In addition, we analyzed the transcriptome from lung and liver tissues. Results: Exposure to hot water for 7s led to significant systemic and local effects and caused considerable late mortality. Therefore, we used an observation time of 24h in this groups. To study later phases of burns (72h) an exposure time of 6s is optimal. Both conditions led to significant disorganization of collagen, increased oxidative stress, NET formation (by immunodetection of H3cit, NE, MPO), apoptosis (cC3) and alterations of the levels of DNase1 and DNase1L3. Transcriptome analysis revealed remarkable alterations in genes involved in acute phase signaling, cell cohesion, extracellular matrix organization, and immune response. Conclusion: We identified two scald models that allow the analysis of early (24h) or late (72h) severe burn effects, thereby generating reproducible and standardized scald injuries. The study elucidated the important involvement of neutrophil activity and the role of NETs in burns. Extensive transcriptome analysis characterized the acute phase and tissue remodeling pathways involved in the process of healing and may serve as crucial basis for future in-depth studies.

Midgut Volvulus Adds a Murine, Neutrophil-Driven Model of Septic Condition to the Experimental Toolbox.

BACKGROUND: Severe infections that culminate in sepsis are associated with high morbidity and mortality. Despite continuous efforts in basis science and clinical research, evidence based-therapy is mostly limited to basic causal and supportive measures. Adjuvant therapies often remain without clear evidence. The objective of this study was to evaluate the septic volvulus ischemia-reperfusion model in comparison to two already established models and the role of neutrophil extacellular traps (NETs) in this model. METHODS: The technique of the murine model of midgut volvulus was optimized and was compared to two established models of murine sepsis, namely cecal ligation and puncture (CLP) and intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). RESULTS: Midgut volvulus for 15 min caused a comparable mortality (38%) as CLP (55%) and peritoneal LPS injection (25%) at 48 h. While oxidative stress was comparable, levels of circulating free DNA (cfDNA), and splenic/hepatic and pulmonary translocation of bacteria were decreased and increased, respectively at 48 h. DNases were increased compared to the established models. Proteomic analysis revealed an upregulation of systemic Epo, IL-1b, Prdx5, Parp1, Ccl2 and IL-6 at 48 h in comparison to the healthy controls. DISCUSSION AND CONCLUSION: Midgut volvulus is a stable and physiological model for sepsis. Depending on the duration and subsequent tissue damage, it represents a combination of ischemia-reperfusion injury and hyperinflammation.

Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 in two new patients with the same homozygous TMCO1 variant and review of the literature.

Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1; OMIM#213980) is a rare autosomal recessive disorder characterized by the clinical triad of developmental delay and/or intellectual disability, a typical facial gestalt with brachycephaly, highly-arched bushy eyebrows, synophrys, hypertelorism, wide nasal bridge, and short nose, as well as multiple vertebrae and rib malformations, such as bifid and fused ribs and abnormal vertebral segmentation and fusion. Biallelic loss-of-function variants in TMCO1 cause CFSMR1. We report on two unrelated Egyptian patients with a phenotype suggestive of CFSMR. Single whole-exome sequencing in patient 1 and Sanger sequencing of TMCO1 in patient 2 revealed the same homozygous TMCO1 nonsense variant c.187C > T/p.(Arg63*) in both affected individuals; patients' healthy parents were heterozygous carriers of the variant. Congenital hearing loss in patients 1 and 2 is an occasional finding in individuals affected by CFSMR. Camptodactyly and syndactyly, which were noted in patient 2, have not or rarely been reported in CFSMR. Review of the literature revealed a total of 30 individuals with the clinically recognizable and unique phenotype of CFSMR1, including the patients reported here, who all carried biallelic TMCO1 variants. Six different TMCO1 variants have been reported in the 30 patients from 14 families, comprising three nonsense, two 2-bp deletions, and a splice donor site variant. All disease-associated TMCO1 variants likely represent null alleles resulting in absence of the encoded protein. TMCO1 has been proposed to act as a Ca2+ channel, while other data revealed TMCO1 as a mitochondrial protein and a component of the translocon at the endoplasmic reticulum, a cellular machinery important for the biogenesis of multi-pass membrane proteins. RAB5IF/C20orf24 has recently been identified as causative gene for craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-2 (CFSMR2; OMIM#616994). Heterodimerization of RAB5IF/C20orf24 and TMCO1 and their interdependence may suggest a pathophysiological role of ER-mitochondria interaction underlying CFSMR.

INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms.

Type I inositol polyphosphate-4-phosphatase (INPP4A) belongs to the group of phosphoinositide phosphatases controlling proliferation, apoptosis, and endosome function by hydrolyzing phosphatidylinositol 3,4-bisphosphate. INPP4A produces multiple transcripts encoding shorter and longer INPP4A isoforms with hydrophilic or hydrophobic C-terminus. Biallelic INPP4A truncating variants cause a spectrum of neurodevelopmental disorders ranging from moderate intellectual disability to postnatal microcephaly with developmental and epileptic encephalopathy and (ponto)cerebellar hypoplasia. We report a girl with the novel homozygous INPP4A variant NM_001134224.2:c.2840del/p.(Gly947Glufs*12) (isoform d). She presented with postnatal microcephaly, global developmental delay, visual impairment, myoclonic seizures, and pontocerebellar hypoplasia and died at the age of 27 months. The level of mutant INPP4A mRNAs in proband-derived leukocytes was comparable to controls suggesting production of C-terminally altered INPP4A isoforms. We transiently expressed eGFP-tagged INPP4A isoform a (NM_004027.3) wildtype and p.(Gly908Glufs*12) mutant [p.(Gly947Glufs*12) according to NM_001134224.2] as well as INPP4A isoform b (NM_001566.2) wildtype and p.(Asp915Alafs*2) mutant, previously reported in family members with moderate intellectual disability, in HeLa cells and determined their subcellular distributions. While INPP4A isoform a was preferentially found in perinuclear clusters co-localizing with the GTPase Rab5, isoform b showed a net-like distribution, possibly localizing near and/or on microtubules. Quantification of intracellular localization patterns of the two INPP4A mutants revealed significant differences compared with the respective wildtype and similarity with each other. Our data suggests an important non-redundant function of INPP4A isoforms with hydrophobic or hydrophilic C-terminus in the brain.

Preclinical patient-derived modeling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease.

The use of mutation analysis of homologous recombination repair (HRR) genes to estimate PARP-inhibition response may miss a larger proportion of responding patients. Here, we provide preclinical models for castration-resistant prostate cancer (CRPC) that can be used to functionally predict HRR defects. In vitro, CRPC LNCaP sublines revealed an HRR defect and enhanced sensitivity to olaparib and cisplatin due to impaired RAD51 expression and recruitment. Ex vivo-induced castration-resistant tumor slice cultures or tumor slice cultures derived directly from CRPC patients showed increased olaparib- or cisplatin-associated enhancement of residual radiation-induced γH2AX/53BP1 foci. We established patient-derived tumor organoids (PDOs) from CRPC patients. These PDOs are morphologically similar to their primary tumors and genetically clustered with prostate cancer but not with normal prostate or other tumor entities. Using these PDOs, we functionally confirmed the enhanced sensitivity of CRPC patients to olaparib and cisplatin. Moreover, olaparib but not cisplatin significantly decreased the migration rate in CRPC cells. Collectively, we present robust patient-derived preclinical models for CRPC that recapitulate the features of their primary tumors and enable individualized drug screening, allowing translation of treatment sensitivities into tailored clinical therapy recommendations.

Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer.

Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.

Clinically Relevant KCNQ1 Variants Causing KCNQ1-KCNE2 Gain-of-Function Affect the Ca2+ Sensitivity of the Channel.

Dominant KCNQ1 variants are well-known for underlying cardiac arrhythmia syndromes. The two heterozygous KCNQ1 missense variants, R116L and P369L, cause an allelic disorder characterized by pituitary hormone deficiency and maternally inherited gingival fibromatosis. Increased K+ conductance upon co-expression of KCNQ1 mutant channels with the beta subunit KCNE2 is suggested to underlie the phenotype; however, the reason for KCNQ1-KCNE2 (Q1E2) channel gain-of-function is unknown. We aimed to discover the genetic defect in a single individual and three family members with gingival overgrowth and identified the KCNQ1 variants P369L and V185M, respectively. Patch-clamp experiments demonstrated increased constitutive K+ conductance of V185M-Q1E2 channels, confirming the pathogenicity of the novel variant. To gain insight into the pathomechanism, we examined all three disease-causing KCNQ1 mutants. Manipulation of the intracellular Ca2+ concentration prior to and during whole-cell recordings identified an impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component. These features were absent in mutant KCNQ1 channels and in wild-type channels co-expressed with calmodulin and exposed to high intracellular Ca2+. Moreover, co-expression of calmodulin with wild-type Q1E2 channels and loading the cells with high Ca2+ drastically increased Q1E2 current amplitudes, suggesting that KCNE2 normally limits the resting Q1E2 conductance by an increased demand for calcified calmodulin to achieve effective channel opening. Our data link impaired Ca2+ sensitivity of the KCNQ1 mutants R116L, V185M and P369L to Q1E2 gain-of-function that is associated with a particular KCNQ1 channelopathy.

Microalgae and Bacteria Interaction-Evidence for Division of Diligence in the Alga Microbiota.

Microalgae are one of the most dominant forms of life on earth that is tightly associated with a distinct and specialized microbiota. We have previously shown that the microbiota of Scenedesmus quadricauda harbors less than 10 distinct microbial species. Here, we provide evidence that dominant species are affiliated with the genera of Variovorax, Porphyrobacter, and Dyadobacter. Experimental and transcriptome-based evidence implies that within this multispecies interaction, Dyadobacter is a key to alga growth and fitness and is highly adapted to live in the phycosphere. While presumably under light conditions the alga provides the energy source to the bacteria, Dyadobacter produces and releases mainly a large variety of polysaccharides modifying enzymes. This is coherent with high-level expression of the T9SS in alga cocultures. The transcriptome data further imply that quorum-quenching proteins (QQ) and biosynthesis of vitamins B1, B2, B5, B6, and B9 are expressed by Dyadobacter at high levels in comparison to Variovorax and Porphyrobacter. Notably, Dyadobacter produces a significant number of leucine-rich repeat (LRR) proteins and enzymes involved in bacterial reactive oxygen species (ROS) tolerance. Complementary to this, Variovorax expresses the genes of the biosynthesis of vitamins B2, B5, B6, B7, B9, and B12, and Porphyrobacter is specialized in the production of vitamins B2 and B6. Thus, the shared currency between partners are vitamins, microalgae growth-promoting substances, and dissolved carbon. This work significantly enlarges our knowledge on alga-bacteria interaction and demonstrates physiological investigations of microalgae and associated bacteria, using microscopy observations, photosynthetic activity measurements, and flow cytometry. IMPORTANCE The current study gives a detailed insight into mutualistic collaboration of microalgae and bacteria, including the involvement of competitive interplay between bacteria. We provide experimental evidence that Gram-negative bacteria belonging to the Dyadobacter, Porphyrobacter, and Variovorax are the key players in a Scenedesmus quadricauda alga-bacteria interaction. We impart strong evidence that Dyadobacter produces and releases polysaccharides degradation enzymes and leucine-rich repeat proteins; Variovorax supplies the consortium with auxins and vitamin B12, while Porphyrobacter produces a broad spectrum of B vitamins. We show not only that the microalgae collaborate with the bacteria and vice versa but also that the bacteria interact with each other via quorum-sensing and secretion system mechanisms. The shared currency between partners appears to be vitamins, microalgae growth-promoting substances, and dissolved carbon.

Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice.

Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring's developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life.